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ABSTRACT: Melanocytic lesions with spitzoid differentiation represent a difficult management paradigm. Spitzoid lesions form a spectrum of distinct entities encompassing Spitz naevi, atypical Spitz naevi and spitzoid melanoma which range from benign to malignant. Differentiation between benign and malignant lesions can be challenging making surgical management difficult. In this article we highlight clinical conundrums regarding Spitz naevi. We review the literature in terms of the newer histological tools available to more explicitly classify these lesions which may have an impact on the clinical care that these patients receive. The article also examines the controversy which surrounds the role of sentinel lymph node biopsy (SLNB) and completion lymph node dissection in the management of melanocytic proliferations with Spitz differentiation.
The surgeon: journal of the Royal Colleges of Surgeons of Edinburgh and Ireland 03/2013; · 1.41 Impact Factor
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ABSTRACT: Junctional adhesion molecule-A (JAM-A) is a membranous cell-cell adhesion protein involved in tight-junction formation in epithelial and endothelial cells. Its overexpression in breast tumors has recently been linked with increased risk of metastasis. We sought to identify if JAM-A overexpression was associated with specific subtypes of breast cancer as defined by the expression of human epidermal growth factor receptor-2 (HER2), estrogen receptor (ER) and progesterone receptor. To this end, JAM-A immunohistochemistry was performed in two breast cancer tissue microarrays. In parallel, cross-talk between JAM-A, HER2 and ER was examined in several breast cell lines, using complementary genetic and pharmacological approaches. High JAM-A expression correlated significantly with HER2 protein expression, ER negativity, lower patient age, high-grade breast cancers, and aggressive luminal B, HER2 and basal subtypes of breast cancer. JAM-A and HER2 were co-expressed at high levels in vitro in SKBR3, UACC-812, UACC-893 and MCF7-HER2 cells. Knockdown or functional antagonism of HER2 did not alter JAM-A expression in any cell line tested. Interestingly, however, JAM-A knockdown decreased HER2 and ER-α expression, resulting in reduced levels of phospho-(active) AKT without an effect on the extracellular signal-related kinase phosphorylation. The downstream effects of JAM-A knockdown on HER2 and phospho-AKT were partially reversed upon treatment with the proteasomal inhibitor MG132. We conclude that JAM-A is co-expressed with HER2 and associates with aggressive breast cancer phenotypes. Furthermore, we speculate that JAM-A may regulate HER2 proteasomal degradation and activity, potentially offering a promise as a therapeutic target in HER2-positive breast cancers.Oncogene advance online publication, 2 July 2012; doi:10.1038/onc.2012.276.
Oncogene 07/2012; · 6.37 Impact Factor
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ABSTRACT: Identification of HER-2/NEU — PEA3 positive patients may have important implications in the treatment of breast cancer and
could prove an appropriate therapeutic target.
Irish Journal of Medical Science 05/2012; 171:21-21. · 0.58 Impact Factor
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ABSTRACT: Accurate pre-operative localisation is now possible, enabling a more directed unilateral exploration to be performed with
a similar high success rate to bilateral neck exploration.
Irish Journal of Medical Science 04/2012; 171:34-34. · 0.58 Impact Factor
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Irish Journal of Medical Science 04/2012; 171:21-21. · 0.58 Impact Factor
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ABSTRACT: These findings suggest aspirin and meloxicam modulate breast cancer cells survival by interfering both cell cycle independent
(mitochondrial Bcl-2) and cycle-dependent (survivin) apoptotic pathways. The COX inhibitors efficiently prevented the cdc2-survivin
complex activation by reducing the phosphorylation of cdc2 and c-raf. They modulate the anti-apoptotic effect of bFGF independent
of COX II activities. The anti-survivin properties of aspirin and meloxicam in our in vitro model may explain the chemoprevention
role of COX inhibitors.
Irish Journal of Medical Science 04/2012; 171:16-17. · 0.58 Impact Factor
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Irish Journal of Medical Science 04/2012; 174:53-54. · 0.58 Impact Factor
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ABSTRACT: BackgroundWith the increasing incidence of breast cancer in patients over 70 years, there is interest in the best therapeutic approach.
AimsTo review the management of breast cancer in elderly women and to identify the factors involved in the decision to treat patients
with tamoxifen as first line therapy.
Patients and methodsBetween 1986 and 1999, 302 female patients aged ≥ 70 years presented with primary breast cancer, of whom 219 underwent surgery,
79 received tamoxifen as first line treatment and four received primary radiotherapy. A retrospective review was performed
on these 79 patients and the outcome recorded.
ResultsOf these 79 patients, data was available on 68. Follow-up ranged from one to 63 months (median 17 months). Co-morbidity was
the principal reason for choosing first line tamoxifen therapy in 61% and patient preference in 11%. Tumour size was less
than 5cm in 51%. In 25% tumour size decreased, in 24% it remained stable and in 27% it increased in size following tamoxifen
therapy. Additional treatment was prescribed for 33% of patients.
ConclusionIn the authors’ experience, for those elderly patients suffering considerable co-morbidity or who refuse surgical intervention,
tamoxifen is an acceptable alternative.
Irish Journal of Medical Science 04/2012; 171(1):28-30. · 0.58 Impact Factor
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Irish Journal of Medical Science 04/2012; 174:32-33. · 0.58 Impact Factor
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ABSTRACT: INTRODUCTION: Recent decades have seen a significant shift towards conservative management of the axilla. Increasingly, immunohistochemical analysis of sentinel nodes leads to the detection of small tumour deposits, the significance of which remains uncertain. The aims of this study are to examine patients whose sentinel lymph nodes are positive for macro-metastasis, micro-metastasis or isolated tumour cells (ITCs) and to determine the rate of further nodal disease after axillary lymph node dissection (ALND). METHODS: A retrospective analysis of all patients undergoing a sentinel lymph node biopsy (SLNB) between January 2007 and December 2010 in a tertiary referral breast unit was performed. Patients who underwent an axillary lymph node dissection for macro-metastasis, micro-metastasis or ITCs were identified. Demographics, histological data and the rate of further axillary disease were examined. RESULTS: In total, 664 breast cancer patients attended the symptomatic breast unit during the study period, 360 of whom underwent a SLNB. Seventy patients had a SLNB positive for macro-metastasis. All of these patients underwent ALND. A positive SLNB with either micro-metastasis or ITCs was identified in 58 patients. Only 41 of the 58 patients went on to have an ALND, due primarily to variations in surgeons' preferences. Nineteen patients with micro-metastasis underwent an ALND. Four patients had further axillary disease (21%). Twenty-two patients had ITCs identified, of whom only one had further disease (4.5%). No statistically significant difference was found between the two groups in terms of tumour size, grade, lymphovascular invasion or oestrogen receptor status. CONCLUSION: ALND should be considered in patients with micro-metastasis at SLNB. It should rarely be employed in the setting of SLNB positive for ITCs.
The surgeon: journal of the Royal Colleges of Surgeons of Edinburgh and Ireland 02/2012; · 1.41 Impact Factor
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ABSTRACT: Studies show internet sourced information often has poor accuracy. However, it is rapidly becoming a major source of patient information. Our aim was to assess accuracy of breast cancer-related information on the internet. The top five breast cancer-related search terms were identified using the commercial program "Wordtracker". These terms were searched using the search-engine "Google" and the top 100 webpages per topic analysed for applicability and accuracy of information. Overall 500 webpages were analysed. 42% were inapplicable to the question asked. Applicable accuracy rates were variable amongst the five terms: "breast cancer symptoms" 84%, "breast cancer care" 87%, "breast cancer stage" 88%, "breast cancer survival" 91% and "breast cancer signs" 78%. Educational websites were more likely to be accurate(p < 0.001) and interest group administered websites less likely to be accurate(p = 0.018) than other websites. Finding accurate breast cancer information on the internet is difficult due to large numbers of inapplicable unregulated websites preferentially returned via search engines.
Breast (Edinburgh, Scotland) 02/2012; 21(4):514-7. · 2.09 Impact Factor
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The surgeon: journal of the Royal Colleges of Surgeons of Edinburgh and Ireland 02/2012; 10(5):301-2. · 1.41 Impact Factor
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ABSTRACT: Surveillance of Clostridium difficile infection (CDI) is an essential component of a CDI preventative programme.
The aim of this study was to evaluate two methods of CDI surveillance.
Prevalence of CDI, antibiotic use and associated co-morbidity was assessed weekly on two wards over 6 weeks. In addition, CDI incidence surveillance was performed on all new CDI cases over a 13-week period. Cases were assessed for CDI risk factors, disease severity, response to treatment and outcome at 6 months.
Clostridium difficile infection prevalence was 3.5% (range 2.9-6.1%) on the medical ward and 1.1% (range 0-3.5%) on the surgical ward. Patients on the medical ward were older and more likely to be colonised with MRSA; however, recent antibiotic use was more prevalent among surgical patients. Sixty-one new CDI cases were audited. Patients were elderly (mean age 71 years) with significant co-morbidity (median age adjusted Charlson co-morbidity score 5). CDI ribotypes included 027 (29 cases) 078 (5) and 106 (4). Eight patients developed severe CDI, seven due to 027. Antibiotic use was common with 56% receiving three or more antibiotics in the preceding 8 weeks. Twenty-four patients had died at 6 months, five due to CDI.
Clostridium difficile infection prevalence gives a broad overview of CDI and points to areas that require more detailed surveillance and requires little time. However, patient-based CDI incidence surveillance provides a more useful analysis of CDI risk factors, disease and outcome for planning preventative programmes and focusing antibiotic stewardship efforts.
Irish Journal of Medical Science 02/2012; 181(3):315-20. · 0.58 Impact Factor
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ABSTRACT: Obtaining a place in an Irish medical school is extremely competitive, a situation mirrored in many other countries. We aimed to determine the factors influencing school students in deciding to study medicine in university. We further determined what level of interest exists in pursuing a surgical career after completion of medical school.
The Royal College of Surgeons in Ireland hosts an annual "Introduction to Medicine" programme for senior school children. Attendees were surveyed using a Likert scale to examine the factors influencing the group in choosing to study medicine, and pursue surgery as their ultimate career choice.
A total of 128 completed the survey, giving a response rate of 100%. The opportunity to help others was most the most influential factors cited by students (97%). Males were significantly more likely to have an interest in a career in surgery rather than medicine (p = 0.003), and ranked "financial reward" (p = 0.036) as a more significant factors in influencing career choice than did females.
A clear understanding of these factors influencing our students in their career choices and a strategy of recruitment based on these is imperative in order to optimize recruitment of students most suited to working as doctors.
The surgeon: journal of the Royal Colleges of Surgeons of Edinburgh and Ireland 08/2011; 9(4):191-4. · 1.41 Impact Factor
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ABSTRACT: Cutaneous melanoma is an aggressive disease. S100beta is an established biomarker of disease progression; however, the mechanism of its regulation in melanoma is undefined.
Expression of HOXC11 and SRC-1 was examined by immunohistochemistry and immunofluorescence. Molecular and cellular techniques were used to investigate regulation of S100beta, including, western blot, qPCR, ChIP and migration assays.
Expression levels of the transcription factor HOXC11 and its coactivator SRC-1 were significantly elevated in malignant melanoma in comparison with benign nevi (P<0.001 and P=0.017, respectively, n=80), and expression of HOXC11 and SRC-1 in the malignant tissue associated with each other (P<0.001). HOXC11 recruitment to the promoter of S100beta was observed in the primary melanoma cell line SKMel28. S100beta expression was found to be dependant on both HOXC11 and SRC-1. Treatment with the Src/Abl inhibitor, dasatinib, reduced HOXC11-SRC-1 interaction and prevented recruitment of HOXC11 to the S100beta promoter. Dasatinib inhibited both mRNA and protein levels of S100beta and reduced migration of the metastatic cell line MeWo.
We have defined a signalling mechanism regulating S100beta in melanoma, which can be modulated by dasatinib. Profiling patients for expression of key markers of this network has the potential to increase the efficacy of dasatinib treatment.
British Journal of Cancer 06/2011; 105(1):118-23. · 5.04 Impact Factor
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ABSTRACT: Sleep deprivation is an established part of the working life for Non-Consultant Hospital Doctors (NCHDs) in Ireland. Concern exists about the effect of extended NCHD work hours. We utilised a Nintendo Wii to evaluate motor function of NCHDs both prior to their on-call shift and the day afterwards. Data was exported to SPSS ver. 15 for statistical analysis with p < 0.05 considered significant. A total of 72 NCHDs were invited to participate in this study. There was a 62.5% (45) rate of follow-up. Overall 27 (60%) NCHDs were on medical call, with 18 (40%) on surgical call. There was no statistically significant difference between NCHDs pre-and post-call motor assessment scores. The majority of study participants (75.5%, n = 34) had four or more hours sleep. On-call duty allows for a greater than anticipated amount of sleep per on-call shift and therefore has a negligible effect on the motor skills of medical staff.
Irish medical journal 06/2011; 104(6):171-3.
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ABSTRACT: Surgical patients are at particular risk of healthcare-associated infection (HCAI) due to the presence of a surgical site leading to surgical site infection (SSI), and because of the need for intravascular access resulting in catheter-related bloodstream infection (CRBSI). A two-year initiative commenced with an initial audit of surgical practice; this was used to inform the development of a targeted educational initiative by surgeons specifically for surgical trainees. Parameters assessed during the initial audit and a further audit after the educational initiative were related to intra- and postoperative aspects of the prevention of SSIs, as well as care of peripheral venous catheters (PVCs) in surgical patients. The proportion of prophylactic antibiotics administered prior to incision across 360 operations increased from 30.0% to 59.1% (P<0.001). Surgical site dressings were observed in 234 patients, and a significant decrease was found in the percentage of dressings that were tampered with during the initial 48h after surgery (16.5% vs 6.2%, P=0.030). In total, 574 PVCs were assessed over the two-year period. Improvements were found in the proportion of unnecessary PVCs in situ (37.9% vs 24.4%, P<0.001), PVCs in situ for >72h (10.6% vs 3.1%, P<0.001) and PVCs covered with clean and intact dressings (87.3% vs 97.6%, P<0.001). Significant improvements in surgical practice were established for the prevention of SSI and CRBSI through a focused educational programme developed by and for surgeons. Potentially, other specific measures may also be warranted to achieve further improvements in infection prevention in surgical practice.
The Journal of hospital infection 06/2011; 78(4):312-6. · 3.01 Impact Factor
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ABSTRACT: A predominance of melanomas on the left side of the body has recently been described. No associations between tumour laterality and gender, age or anatomical site have been identified.
The aim of this study was to investigate the prevalence of left-sided melanomas in an Irish population and to examine potential associations with various patient and tumour characteristics.
A retrospective chart review of patients with cutaneous melanoma who were treated over a 10-year period was carried out. Lateral distribution of melanoma on either side of the body was compared using χ(2) analysis and evaluated by gender, age group, anatomic location, histologic subtype and Breslow depth.
More melanomas occurred on the left side (57%, P = 0.015), and this finding was particularly significant in females. For both genders combined, there were no statistically significant differences in laterality by age group, anatomic location, type of melanoma and Breslow depth. There were significantly more superficial spreading melanomas on the left side in both men and women.
This study demonstrates a predominance of left-sided melanomas in Irish patients. While a number of demographic and molecular associations have been proposed, further research is required to fully explain this phenomenon.
Irish Journal of Medical Science 04/2011; 180(3):727-30. · 0.58 Impact Factor
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ABSTRACT: The use of a minimally invasive approach to treat appendicitis has yet to be universally accepted. The objective of this study was to examine recent trends in Ireland in the surgical management of acute appendicitis.
Data were obtained from the Irish Hospital In-Patient Enquiry system for patients discharged with a diagnosis of appendicitis between 1999 and 2007. An anonymous postal survey was sent to all general surgeons of consultant and registrar level in Ireland to assess current attitudes to the use of laparoscopic appendectomy.
The use of laparoscopic appendectomy increased throughout the study and was the most common approach for appendectomy in 2007. Multivariate analysis revealed age under 50 years (OR = 1.51), female sex (OR = 2.84) and residence in high-density population areas (OR = 4.15) as predictive factors for undergoing laparoscopic appendectomy in the most recent year of the study. While 97% of surgeons reported current use of laparoscopy in patients with acute right iliac fossa pain, in most cases it was selective. Surgeons in university teaching hospitals (42 of 77; 55%) were more likely to report using laparoscopic appendectomy for all cases of appendicitis than those in regional (six of 23; 26%) or general (13 of 53; 25%) hospitals (P = 0.048).
This study has demonstrated a significant increase in laparoscopic appendectomy, yet a variety of patient and surgeon factors contribute to the choice of procedure. Differences in the perception of benefit of the laparoscopic approach amongst surgeons appears to be an important factor in determining the operative approach for appendectomy.
Colorectal Disease 03/2011; 14(2):243-9. · 2.93 Impact Factor
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ABSTRACT: Approximately five percent of patients who undergo surgery develop surgical site infections (SSIs) which are associated with an extra seven days as an inpatient and with increased postoperative mortality. The competence and technique of the surgeon is considered important in preventing SSI. We have reviewed the evidence on different aspects of surgical technique and its role in preventing SSI. The most recent guidelines from the National Institute for Health and Clinical Excellence in the UK recommend avoiding diathermy for skin incision even though this reduces incision time and blood loss, both associated with lower infection rates. Studies comparing different closure techniques, i.e. continuous versus interrupted sutures, have not found a statistically significant difference in the SSI rate, but using continuous sutures is quicker. For contaminated wounds, the surgical site should be left open for four days to allow for treatment of local infection before subsequent healing by primary intention. Surgical drains should be placed through separate incisions, closed suction drains are preferable to open drains, and all drains should be removed as soon as possible. There are relatively few large studies on the impact of surgical techniques on SSI rates. Larger multicentre prospective studies are required to define what aspects of surgical technique impact on SSI, to better inform surgical practice and support education programmes for surgical trainees.
The Journal of hospital infection 02/2011; 78(1):1-4. · 3.01 Impact Factor
